Varicella zoster virus (VZV) is a ubiquitous infectious agent. The natural history pathophysiology, and effective therapy of the clinical diseases are only partially characterized by functional and molecular assays. Varicella is the most common infectious disease in the USA. Reactivated "latent" VZV infection, herpes zoster, is a widespread, often debilitating disease especially in the elderly or immunocompromised patient. Of the estimated 300,000 new cases of zoster annually in this country, nearly 56,000 involve the eye with more than 50-% of patients suffering visual loss as a result of acute or chronic disease. The development of the guinea pig model of ocular VZV infection and analysis by virus recovery, clinical, and molecular biology techniques has allowed for characterization of VZV-induced ocular and systemic disease processes. Long-term objectives of this application are to investigate the presence of VZV DNA and evaluate the activity of the VZV genome (VZV RNA production) in neuronal (trigeminal ganglia) and exraneuronal ((ocular) tissues during acute, latent, and reactivating infection in the guinea pig and rabbit VZV infection models. Specific aims include: (1) detection of VZV DNA and sense and antisense VZV RNA to Immediate Early, Early and other VZV gene areas by hybridization in ocular and CNS tissues, (2) analysis of VZV RNA-induced proteins (ie, role of VZV RNA during latency, and (3) evaluation of currently available and new antiviral agents during acute and reactivating VZV infection. All proposed studies will utilize clinical parameters, VZV recovery assays, and sensitive molecular virology dot/slot, in situ, Northern, and Western blot techniques to characterize the VZV host-cell interactions and VZV-induced translational products during VZV infection stages. In addition, the polymerase chain reaction technique will be used to amplify selectively VZV DNA and VZV RNA in situ and in nucleic acid extraction studies and will allow for investigation of VZV DNA and VZV RNA retained in low copy umber. Knowledge of VZV host-cell interactions will led to more effective therapies to combat the devastating ocular and systemic effects of VZV reactivating infection in both immunocompetent and the increasing population of immunocompromised AIDS, blood dyscrasia, and organ transplant patients.